1. Field of the Invention
The present invention relates to a particle pattern judging method, in which a specimen and a reagent are mixed in a reaction vessel to cause an immunological agglutinating reaction therein, and a particle pattern formed on the bottom surface of the reaction vessel is measured in an optical manner to be automatically judged whether the particle pattern is agglutinated or not and the other property of the pattern on a clinic purpose.
2. Prior Art Statement
In Japanese Patent Laid-open Publication No. 58-105065, there is disclosed a conventional particle pattern judging method in which the particle pattern formed on the bottom surface of the reaction vessel by the agglutinating reaction is measured in an optical manner and a ratio in brightness between a central portion of the reaction vessel and a peripheral portion thereof is obtained to judge whether the particle pattern is agglutinated or not on the basis of the ratio. Such technique for judging particle patterns is also disclosed in U.S. Pat. No. 4,727,033, in which light intensities of central and peripheral portions of the inclined bottom surface of the reaction vessel are separately measured by using two light receiving elements and the judgement whether the particle pattern formed on the bottom surface is agglutinated or not is conducted on the basis of a ratio between the output of the light receiving element for measuring the light intensity of the central portion of the bottom surface and the output of the light receiving element for measuring the light intensity of the peripheral portion thereof. That is to say, when the particle pattern is agglutinated, the particles are uniformly deposited on the bottom surface of the reaction vessel so that the difference between the light intensities of the light receiving elements is small; in contrast thereto, when the particle pattern is not agglutinated, the particles are fallen down the inclined bottom surface of the reaction vessel and collected in the central portion thereof so that the difference between the light intensities of these two light receiving elements becomes large. In such conventional particle pattern judging method, the thus obtained ratio is compared with predetermined upper and lower limits; and when the ratio is larger than the upper limit, the particle pattern is judged as an agglutinated pattern, when the ratio is smaller than the lower limit, the particle pattern is judged as a non-agglutinated pattern, and when the ratio is between the upper and lower limits, the particle pattern is judged as ambiguous and thus it is impossible to judge the ambiguous pattern.
Further, in Japanese Patent Laid-open Publication Nos. 61-215948, 62-105031, 63-58237 and 63-256839, there is disclosed another particle pattern judging method in which agglutinating reactions are conducted in a number of wells formed in a microplate and an optical image of the wells is picked up by a television camera; the image data of each well is processed by a computer to obtain an area where the particles are deposited on the bottom surface of each well and the particle pattern is judged whether it is agglutinated or not on the basis of the thus obtained area.
According to the method disclosed in Japanese Patent Preliminarily Laid-open Publication No. 63-58237, an image of bottom surface of each well formed in the microplate is picked up by a television camera to obtain image signals thereof; data of a center point of the well is obtained by processing the thus obtained image signals; then a contour of particle pattern formed in the well is obtained by obtaining the difference in brightness between the image signal inside of a circle, which is formed around the center point, and the image signal outside of the circle; then the area inside the thus obtained contour is obtained; this area is then compared with a predetermined standard value. When the area is larger than the standard value, the particle pattern is judged as an agglutinated pattern and when the area is smaller than the standard value, the particle pattern is judged as a non-agglutinated pattern. That is to say, in this conventional method, the particle pattern is judged by the number of pixels corresponding to the particles collected in the center portion of the well.
Further, in Japanese Patent Preliminarily Laid-open Publication No. 63-256839, there is disclosed another judging method, in which the center point of the well is obtained in the same way mentioned above; and the judgement is conducted by utilizing a relative relation between a dimension of the center portion, where the particle are deposited, on the bottom surface of the reaction vessel and a standard deviation of a differential coefficient of the particle pattern.
However, in the above mentioned conventional methods, there is a drawback that it is not possible to judge whether the particle pattern is agglutinated or not in an exact manner. In case the agglutination force of the particles to be tested is so weak that there is a great possibility that an agglutinated pattern having almost the same shape as that of a non-agglutinated pattern is formed on the bottom surface of the reaction vessel: it is very difficult to automatically judge such particle patterns exactly. Therefore, in the conventional method, the reliability of judgement is so low that an operator has to check the patterns in a visual manner and correct the result judged by an automatic particle pattern judgement apparatus. Additionally much labor is therefore necessary. In the method disclosed in JP 58-105065 and U.S. Pat. No. 4,272,033, there is a problem that the number of specimens which are judged as ambiguous becomes large, because, the agglutinating reaction is generally very delicate so that there are many cases where the ambiguous particle patterns are formed. Therefore, efficiency in processing the specimens decreases and human mistakes occur frequently. Thus, an analysing accuracy and a reliability of the judgement are decreased.
In the method disclosed in Japanese Patent Preliminarily Laid-open Publication No. 63-58237, it is possible to determine the central point of the particle pattern exactly, but a dimension of the portion where the particles are deposited on the bottom surface of the vessel not only depends upon whether the particles are agglutinated or not but also depends upon the amount of the specimen or the reagent. Therefore, it is very difficult to conduct an exact judgement.
Furthermore, in the method disclosed in Japanese Patent Preliminarily Laid-open Publication No. 63-256839, the judgement result is apt to be influenced by bubbles included in the test liquid as well as the fact that the pattern gets out of its shape or the pattern is torn; thus it is also impossible to judge the pattern exactly.